The long term goals of this study: a) to gain a better understanding of the enzymes catalyzing the metabolism of prostaglandins and of factors regulating the activity of these enzymes, b) to determine whether abnormalities in these enzymes are involved in the pathogenesis of any disease state, and c) to develop and test compounds in vitro, which possess a pharmacologic potential because they react with the enzymes catalyzing the early steps of prostaglandin metabolism. To enable us to achieve these goals we plan: a) to determine the effect of preeclampsia/eclampsia and of diabetes mellitus on these enzymes, b) to determine the effect of salt intake on the rabbit kidney 9-ketoprostaglandin reductase activity c) to synthesize qlutathione thiosulfinate and its analogs, d) to study the active-sites of these enzymes, e) to develop reversible and irreversible inhibitors of specific prostaglandin metabolizing enzymes, f) to test synthetic prostaglandins and thromboxanes, and g) to purify and characterize the placental 9-hydroxy-prostaglandin dehydrogenase.